We propose to characterize more fully a protein (probably a macroglobulin) from human blood serum which we have shown to increase lactate production in chicken erythrocytes and to cause hemolysis. Procedures to be used for purification include gel filtration, cellulose ion-exchange chromatography, starch gel electrophoresis and hanging-curtain paper electrophoresis. Homogeneity will be tested by means of polyacrylamide gel electrophoresis, immunoelectrophoresis and ultracentrifugation. Biological activities to be assayed are stimulation of lactate production in chicken erythrocytes, stimulation of tryptophan uptake in the same cells and hemolysis. We plan to compare the properties of this protein or proteins with those of proteins isolated by other workers from serum of schizophrenic individuals. When we have adequately described this protein or proteins and been able to devise reliable testing procedures for detection, we plan to conduct carefully controlled studies to determine the incidence of such materials in the blood sera of schizophrenic subjects, nonschizophrenic psychiatric patients and normal individuals in order to further evaluate the relationship of such materials to schizophrenia. In addition, we plan to begin a more thoroughgoing study of the effects of serum macroglobulins on membrane function, such as mediated transport and passive permeability.